Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis
- PMID: 15793006
- PMCID: PMC556003
- DOI: 10.1073/pnas.0500941102
Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis
Erratum in
-
Correction for Hui et al., Three distinct kinetic groupings of the synaptotagmin family: Candidate sensors for rapid and delayed exocytosis.Proc Natl Acad Sci U S A. 2024 Jan 16;121(3):e2321505121. doi: 10.1073/pnas.2321505121. Epub 2024 Jan 12. Proc Natl Acad Sci U S A. 2024. PMID: 38215188 Free PMC article. No abstract available.
Abstract
Synaptotagmins (syts) are a family of membrane proteins present on a variety of intracellular organelles. In vertebrates, 16 isoforms of syt have been identified. The most abundant isoform, syt I, appears to function as a Ca2+ sensor that triggers the rapid exocytosis of synaptic vesicles from neurons. The functions of the remaining syt isoforms are less well understood. The cytoplasmic domain of syt I binds membranes in response to Ca2+, and this interaction has been proposed to play a key role in secretion. Here, we tested the Ca(2+)-triggered membrane-binding activity of the cytoplasmic domains of syts I-XII; eight isoforms tightly bound to liposomes that contained phosphatidylserine as a function of the concentration of Ca2+. We then compared the disassembly kinetics of Ca2+.syt.membrane complexes upon rapid mixing with excess Ca2+ chelator and found that syts can be classified into three distinct kinetic groups. syts I, II, and III constitute the fast group; syts V, VI, IX, and X make up the medium group; and syt VII exhibits the slowest kinetics of disassembly. Thus, isoforms of syt, which have much slower disassembly kinetics than does syt I, might function as Ca2+ sensors for asynchronous release, which occurs after Ca2+ domains have collapsed. We also compared the temperature dependence of Ca2+.syt.membrane assembly and disassembly reactions by using squid and rat syt I. These results indicate that syts have diverged to release Ca2+ and membranes with distinct kinetics.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/556003/bin/zpq0130578280001.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/556003/bin/zpq0130578280002.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/556003/bin/zpq0130578280003.gif)
Similar articles
-
Synaptotagmin V is targeted to dense-core vesicles that undergo calcium-dependent exocytosis in PC12 cells.J Biol Chem. 2002 Jul 5;277(27):24499-505. doi: 10.1074/jbc.M202767200. Epub 2002 May 2. J Biol Chem. 2002. PMID: 12006594
-
Synaptotagmin regulates mast cell functions.Immunol Rev. 2001 Feb;179:25-34. doi: 10.1034/j.1600-065x.2001.790103.x. Immunol Rev. 2001. PMID: 11292024 Review.
-
Calcium-dependent and -independent hetero-oligomerization in the synaptotagmin family.J Biochem. 2000 Oct;128(4):637-45. doi: 10.1093/oxfordjournals.jbchem.a022796. J Biochem. 2000. PMID: 11011146
-
Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth.Chem Phys Lipids. 1999 Apr;98(1-2):59-67. doi: 10.1016/s0009-3084(99)00018-3. Chem Phys Lipids. 1999. PMID: 10358928 Review.
-
Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins.Nature. 1995 Jun 15;375(6532):594-9. doi: 10.1038/375594a0. Nature. 1995. PMID: 7791877
Cited by
-
A minimal presynaptic protein machinery mediating synchronous and asynchronous exocytosis and short-term plasticity.bioRxiv [Preprint]. 2024 Apr 18:2024.04.15.589559. doi: 10.1101/2024.04.15.589559. bioRxiv. 2024. PMID: 38659918 Free PMC article. Preprint.
-
Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion.Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2320505121. doi: 10.1073/pnas.2320505121. Epub 2024 Apr 3. Proc Natl Acad Sci U S A. 2024. PMID: 38568977 Free PMC article.
-
Synaptotagmin 7 docks synaptic vesicles to support facilitation and Doc2α-triggered asynchronous release.Elife. 2024 Mar 27;12:RP90632. doi: 10.7554/eLife.90632. Elife. 2024. PMID: 38536730 Free PMC article.
-
Synaptotagmin-7 Counteracts Short-Term Depression during Phasic Dopamine Release.eNeuro. 2024 Mar 12;11(3):ENEURO.0501-23.2024. doi: 10.1523/ENEURO.0501-23.2024. Print 2024 Mar. eNeuro. 2024. PMID: 38365841 Free PMC article.
-
Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration.Nat Commun. 2023 Nov 27;14(1):7761. doi: 10.1038/s41467-023-42497-8. Nat Commun. 2023. PMID: 38012142 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous